The specific aims for the COBRE for Perinatal Biology are to continue our scientific contributions to the field of perinatal biology and to further development of the research enterprise at Women &Infants Hospital. The common theme of this proposal is that mechanisms for regulation of development during the fetal or early postnatal period can inform importantly the regulatory mechanisms governing cell function, organ maturation, health and disease in later life. This theme is highlighted in the projects will support: 1) host pathogen interactions, developmental immunology and the molecular pathogenesis of yeast infections of Candida albicans in the preterm infant;2) DMA methylation and chromatin remodeling as a biomolecular "fingerprint" in the placenta for adverse intrauterine life and fetal programming;3) the role of hypoxia and hypoxia-regulated genes in early embryogenesis and implantation;4) recapitulation of the "fetal gene program" during stem cell repair of cardiac injury in adult life;5) the immunopathogenesis of preeclampsia;6) role of natural killer cells in successful pregnancy outcomes. The programmatic aims of this COBRE are to continue to provide scientific and career mentorship to Junior Faculty in an interdisciplinary environment that fosters creativity and transdisciplinary collaboration in scientific approaches. Using resources from our prior period of support we have developed a robust perinatal research center in the Kilguss Research Institute which has become a state-of-the-art research facility. It houses the majority of this group of junior scientists, all of whom have demonstrated excellent potential for independent careers, as well as successful, senior investigators. This award will allow us to continue to leverage our programs and the environment we have created into the kinds of support needed by all junior investigators to become successful independent investigators. The award will allow them to collaborate with leading scientists in their fields and to utilize contemporary approaches in cell and molecular biology to address important issues in perinatal and developmental biology. The combination of a supportive environment within a robust setting of inquiry and exploration will allow us to enhance/ensure their career trajectories as independent investigators. The clinical relevance of these areas is borne out by their high likelihood to identify important mechanisms during development which inform the pathogenesis of disease across the life spectrum. This program is based at the Women &Infants Hospital of Rhode Island. It will provide support for four full projects and 2 pilot projects of Junior Faculty who will me mentored by established investigators from. An outstanding group of investigators from other centers will provide support and collaboration as the External Scientific Advisory Committee.